Placebo Controlled Trial of Sodium Selenite and Procalcitonin Guided Antimicrobial Therapy in Severe Sepsis

Septic Shock Clinical Trial

— SISPCT  

Official title:

Prospective, Randomized Multicenter Trial of Adjunctive Intravenous Therapy With Sodium-selenite(Selenase®, Double-blinded) and a Procalcitonin Guided Causal Therapy (Open) of Severe Sepsis or Septic Shock.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00832039
• Other study ID #: EudraCT 2007-004333-42
• Secondary ID: 01 KI 01 06SE120
• Status: Completed
• Phase: Phase 3
• First received: January 28, 2009
• Last updated: August 11, 2016
• Start date: November 2009
• Est. completion date: June 2013

Study information

• Verified date: August 2016
• Source: Kompetenznetz Sepsis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

Severe sepsis and septic shock are diseases of infectious origin with a high risk of death. The purpose of this study is to determine whether the intravenous application of selenium (given as sodium-selenite) can reduce mortality in patients with severe sepsis or septic shock. Additionally, it is investigated, whether the measurement of procalcitonin - a marker of infection - can be used to guide anti-infectious measures in this disease.

Description:

This is a multicenter trial of the German Network Sepsis (SepNet) on patients with severe sepsis or septic shock. This study is supported by unrestricted grants.

The release of reactive oxygen species is an important factor in the development of sepsis induced multiorgan dysfunction syndrome. Common protection mechanisms are impaired in this syndrome. Serum levels of selenium, a cofactor of the glutathionperoxidase, are reduced. Several studies suggest a benefit of selenium application in patients with severe sepsis but data from large clinical trials are not available. After inclusion into the study, patients are randomly allocated to a placebo or selenium group. Treating physicians and patients are blinded regarding the allocation. The selenium group receives sodium selenite intravenously

• 1000 µg as a bolus followed by a continuous infusion of 1000 µg per day until the end of ICU treatment but not longer than 21 days.

Procalcitonin (PCT) is a biomarker which is elevated in the blood of patients with severe sepsis/septic shock. Data from patients with community acquired pneumonia demonstrated that this biomarker can be used to decide on the duration of antimicrobial therapy. Studies with small sample size seem to confirm this in ICU patients with severe sepsis. However, this needs to be confirmed in a larger cohort. All patients are randomly allocated to a PCT guided algorithm or a control group. In the PCT-guided group, PCT is measured at randomization, day 4, 7, 10, and 14. Depending on the PCT course, the protocol recommends to change, alter, or stop anti-infectious measures. In the control group, anti-infectious therapy is left to the discretion of the treating physician.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1089
• Est. completion date: June 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Severe sepsis or septic shock according to ACCP/SCCM criteria

• Onset of severe sepsis or septic shock <24 h

• Age >= 18 years

• Informed consent

Exclusion Criteria:

• Pregnant or breast-feeding women

• Fertile female women without effective contraception

• Participation in interventional clinical trial within the last 30 days

• Current participation in any study

• Former participation in this trial

• Selenium intoxication

• No commitment to full patient support (i.e. DNR order)

• Patient's death is considered imminent due to coexisting disease

• Relationship of the patient to study team member (i.e. colleague, relative)

• Infection where guidelines recommend a longer duration of antimicrobial therapy (i.e. endocarditis, tuberculosis, malaria etc)

• Immunocompromised patients

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Sepsis
• Septic Shock
• Severe Sepsis
• Shock
• Shock, Septic
• Toxemia

Intervention

Drug:
• sodium-selenite
An intravenous bolus of 1000 µg followed by a continuous intravenous infusion of 1000 µg/day until patient is discharged from the ICU but not more than 21 applications à 24 hours.
• Placebo
An intravenous bolus of placebo followed by a continuous intravenous infusion with placebo until patient is discharged from the ICU but not more than 21 applications à 24 hours.

Procedure:
• Procalcitonin guided therapy
Causal therapy of sepsis is guided by applying the following algorithm: Day 4: PCT drop from baseline >=50%: no change in causal therapy; PCT drop from baseline <50%: change or optimize antimicrobial therapy, new intervention (i.e. surgery, diagnostics) recommended for source control. Day 7, 10, 14: PCT <=1.0 ng/ml: finish antimicrobial therapy; PCT >1.0 ng/ml and PCT drop from last PCT measurement >=50%: finish antimicrobial therapy; PCT >1.0 ng/ml and PCT drop from last PCT measurement <50%: change or optimize antimicrobial therapy, new intervention (i.e. surgery, diagnostics) recommended for source control.

Locations

Country	Name	City	State
Germany	University Hospital Aachen - Dep. of Intensive Care Medicine	Aachen
Germany	Klinikum Augsburg - Dep. of Anesthesiology and Intensive Care Medicine	Augsburg
Germany	Klinikum Augsburg - Dep. of Medicine I	Augsburg
Germany	Charité Berlin - Campus Virchow-Klinikum - Dep. of Nephrology	Berlin
Germany	Charité Berlin - Dep. of Anesthesiology and Intensive Care Medicine	Berlin
Germany	DRK-Kliniken Berlin-Köpenick - Dep. of Anesthesiology, Pain Therapy, and Intensive Care Medicine	Berlin
Germany	Military Hospital Berlin - Dep. of Anaesthesiology and Intensive Care Medicine	Berlin
Germany	Vivantes Klinikum Neukölln - Dep. of Anesthesiology, Intensive Care Medicine and Pain Therapy	Berlin
Germany	Ev. Krankenhaus Gilead - Dep. of Anesthesiology	Bielefeld
Germany	University Hospital Bonn - Dep. of Anesthesiology and Intensive Care Medicine	Bonn
Germany	Krankenhaus Dresden-Friedrichstadt	Dresden
Germany	University Hospital Dresden - Dep. of Anesthesiology and Intensive Care Med.	Dresden
Germany	HELIOS Klinikum Erfurt - Dep. of Anesthesiology and Intensive Care Medicine	Erfurt
Germany	University Erlangen-Nürnberg - Dep. of Medicine IV	Erlangen
Germany	J.-W. Goethe University Hospital - Dep. of Anaesthesiology, Intensive Care Medicine and Pain Therapy	Frankfurt/Main
Germany	University Hospital Freiburg- Dep. of Surgery	Freiburg
Germany	Georg August Universität Göttingen - Dep. of Anesthesiology and Intensive Care Medicine	Göttingen
Germany	Ernst-Moritz-Arndt-Universität Greifswald - Dep. of Anesthesiology and Intensive Care Medicine	Greifswald
Germany	Martin-Luther-Universität Halle-Wittenberg - Dep. of Anesthesiology	Halle
Germany	University Hospital Halle - Dep. of Medicine III	Halle
Germany	Universitätsklinikum Hamburg-Eppendorf - Dep. of Intensive Care Medicine	Hamburg
Germany	Westküstenklinikum Heide - Dep. of Anesthesiology and Intensive Care Medicine	Heide
Germany	University Hospital Heidelberg - study center Anesthesiology/Surgery	Heidelberg
Germany	University Hospital Jena, Dep. of Anesthesiology and Intensive Care Medicine	Jena
Germany	University Hospital Kiel - Dep. of. Anesthesiology and Intensive Care Medicine	Kiel
Germany	University Hospital Köln - Dep. of Medicine I	Köln
Germany	St. Elisabeth-Krankenhaus - Dep. of Anesthesiology	Köln-Hohenlind
Germany	University Hospital Leipzig - Dep. of Anesthesiology and Intensive Care Medicine	Leipzig
Germany	University Hospital Mannheim - Dep. of Medicine I	Mannheim
Germany	Krankenhaus München-Neuperlach - Dep. of Anesthesiology	München
Germany	Hospital Munich Harlaching - Dep. of Internal Acute Medicine and Prevention	Munich
Germany	University Hospital Munich - Dep. of Anaesthesiology	Munich
Germany	University Hospital Munich - Dep. of Internal Medicine	Munich
Germany	University Hospital Münster - Dep. of Anesthesiology and Intensive Care Medicine	Münster
Germany	Klinikum Oldenburg GmbH - Dep. of Anesthesiology	Oldenburg

Sponsors (3)

Lead Sponsor	Collaborator
Kompetenznetz Sepsis	Biosyn, Brahms AG

Country where clinical trial is conducted

Germany, 

References & Publications (1)

Bloos F, Trips E, Nierhaus A, Briegel J, Heyland DK, Jaschinski U, Moerer O, Weyland A, Marx G, Gründling M, Kluge S, Kaufmann I, Ott K, Quintel M, Jelschen F, Meybohm P, Rademacher S, Meier-Hellmann A, Utzolino S, Kaisers UX, Putensen C, Elke G, Ragaller — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	All cause mortality		28 days	No
Secondary	Mean total SOFA and SOFA subscores		study duration	No
Secondary	All cause mortality		90 days	No
Secondary	Frequency and duration of mechanical ventilation		90 days	No
Secondary	Frequency and duration of vasopressor support		90 days	No
Secondary	Frequency of adverse events and severe adverse events		study duration	Yes
Secondary	Clinical cure and microbiological cure		days 4, 7, 10, 14	No
Secondary	Duration of antimicrobial therapy		study duration	No
Secondary	Costs of antimicrobial therapy		study duration	No
Secondary	Time to change of antibiotic therapy		duration of study	No
Secondary	Days alive without antimicrobial therapy		study duration	No
Secondary	Frequency of resistancies against antibiotics (VRE, MRSA, ESBL)		study duration	Yes
Secondary	ICU length of stay		90 days	No
Secondary	Hospital length of stay		90 days	No
Secondary	Rate of surgical procedures for focus control		study duration	No
Secondary	Rate of procedures to diagnose infections		study duration	No
Secondary	Frequency of new infections		study duration	No

External Links

•   Competence Network Sepsis (SepNet)
•   German Sepsis Society
•   Networks of competence in medicine (an initiative of the German government)
•   Surviving Sepsis Campaign